RRC ID 42640
著者 Nakatsu Y, Kotake Y, Ohta S.
タイトル Tributyltin-induced cell death is mediated by calpain in PC12 cells.
ジャーナル Neurotoxicology
Abstract Tributyltin, an endocrine-disrupting chemical, has been used as a heat stabilizer, agricultural pesticide and component of antifouling paints. In this study, we investigated whether calpain is involved in tributyltin toxicity in undifferentiated PC12 cells. Tributyltin (2 microM) induced an increase of lactate dehydrogenase release, a marker of cytotoxicity, in PC12 cells in a time-dependent manner. It also induced calpain activation in a dose-dependent manner, and a calpain inhibitor, MDL28170 (40 microM), decreased the cellular toxicity, suggesting that calpain is involved in tributyltin toxicity in PC12 cells. Because calpain is a calcium-dependent protease, we examined the effect of EGTA, an extracellular Ca(2+) chelator and BAPTA-AM, an intracellular Ca(2+) chelator. Calpain activation induced by tributyltin was decreased by BAPTA-AM (50 microM), but not by EGTA (1 mM), suggesting that calpain activation is associated with calcium release from intracellular Ca(2+) stores. Further, we investigated the relationship between caspase-3 and calpain. Inhibition of caspase-3 reduced calpain activity induced by tributyltin. In conclusion, we have demonstrated that tributyltin induced cell death through calpain activation, and that intracellular Ca(2+) increase and caspase-3 activation are required for calpain activation by tributyltin.
巻・号 27(4)
ページ 587-93
公開日 2006-7-1
DOI 10.1016/j.neuro.2006.03.010
PII S0161-813X(06)00090-8
PMID 16678266
MeSH Analysis of Variance Animals Calcium / metabolism Calpain / metabolism* Caspase 3 Caspases / metabolism Cell Death / drug effects Cell Survival / drug effects Chelating Agents / pharmacology Cysteine Proteinase Inhibitors / pharmacology Dipeptides / pharmacology Dose-Response Relationship, Drug Egtazic Acid / pharmacology Enzyme Activation / drug effects Fura-2 / pharmacokinetics L-Lactate Dehydrogenase / metabolism PC12 Cells Rats Time Factors Trialkyltin Compounds / metabolism* Trialkyltin Compounds / pharmacology Water Pollutants / metabolism* Water Pollutants / pharmacology
IF 3.105
引用数 23
WOS 分野 TOXICOLOGY PHARMACOLOGY & PHARMACY NEUROSCIENCES
リソース情報
ヒト・動物細胞 PC-12(RCB0009)